Sex differences in cognitive and brain aging: a primate model

描述(申请人提供)：人类大脑和认知的性别差异已经有了很好的记录，但尚不清楚男性和女性是否遵循与年龄相关的认知下降的不同轨迹。确定男性和女性认知老化差异的预测因素可能会导致针对性别的干预措施的发展，以促进两性成功的认知老化。由于人类认知受到社会文化和环境因素的强烈影响，对非人类灵长类动物模型的研究，可以最大限度地减少这种混淆，可以提供相当大的洞察力，了解认知老化中性别差异的生物学基础。这一应用使用了一种翻译灵长类动物模型，该模型特别适合于对常见的绒猴(Callithrix Jacchus)进行神经认知老化的纵向评估。绒猴的寿命约为8年，可以在其整个成年寿命内进行研究。此外，它们还能够执行复杂的认知任务，并经历与年龄相关的大脑变化，这与人类的大脑变化相似。该项目将从中年到老年对完整的雄性和雌性绒猴进行纵向研究。在为期四年的一系列认知、情绪和运动测试中，将对猴子的性别差异和与年龄相关的变化进行评估。每年还将分别使用磁共振成像(MRI)和静息状态功能MRI(FMRI)检查大脑结构和功能连接的性别差异和与年龄相关的变化。将分析以认知受损或未受损为特征的老年猴子大脑中树突棘密度和形态、海马雌二醇水平和�-淀粉样蛋白沉积的性别差异。这项研究应该为从中年到老年的翻译灵长类动物模型中性别和年龄认知差异的生物学相关性提供宝贵的信息。这些数据将成为了解性激素在神经认知老化中的作用的基本基础。归根结底，该项目应该推广针对性别的方法来管理老年人的认知障碍。

DESCRIPTION (provided by applicant): Sex differences in human brain and cognition are well documented, but it remains unclear whether men and women follow different trajectories of age-related cognitive decline. Identifying predictors of differential cognitive aging between men and women could lead to the development of sex-specific interventions to promote successful cognitive aging in both sexes. Because human cognition is strongly influenced by socio- cultural and environmental factors, studies in nonhuman primate models, for which such confounds can be minimized, can provide considerable insight into the biological bases of sex differences in cognitive aging. This application uses a translational primate model uniquely suited for longitudinal assessments of neurocognitive aging, the common marmoset (Callithrix jacchus). With a lifespan of about 8 years, marmosets can be studied throughout their entire adult lifespan. In addition, they are able to perform complex cognitive tasks and experience age-related brain changes that resemble those of humans. This project will study intact male and female marmosets longitudinally from middle-age to old age. Sex differences and age-related changes will be assessed in monkeys tested annually for four years on a battery of cognitive, emotional and motor tests. Sex differences and age-related changes in brain structure and functional connectivity will also be examined annually using Magnetic Resonance Imaging (MRI) and resting- state functional MRI (fMRI), respectively. Sex differences in dendritic spine density and morphology, hippocampal estradiol levels and �-amyloid deposition will be analyzed in the brains of aged monkeys characterized as cognitively impaired or unimpaired. This study should provide invaluable information on the biological correlates of sex and age differences in cognition in a translational primate model followed from middle-age to old age. The data will serve as a fundamental foundation for understanding the role of sex hormones in neurocognitive aging. Ultimately, the project should promote sex-specific approaches to the management of cognitive impairment in older people.